10-125836732-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018180.3(DHX32):c.2187G>A(p.Met729Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_018180.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251442Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135898
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727240
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74490
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.2187G>A (p.M729I) alteration is located in exon 11 (coding exon 11) of the DHX32 gene. This alteration results from a G to A substitution at nucleotide position 2187, causing the methionine (M) at amino acid position 729 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 729 of the DHX32 protein (p.Met729Ile). This variant is present in population databases (rs142010622, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DHX32-related conditions. ClinVar contains an entry for this variant (Variation ID: 1500230). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at